A comparative study on chromium-induced micronuclei assessment in the peripheral blood of Hsd:ICR mice.

This study investigated the genotoxic effects of chromium (Cr) in Hsd:ICR mice, considering factors such as oxidative state, apoptosis, exposure pathway, duration, pregnancy, and transplacental exposure. Genotoxicity was assessed using the erythrocytes' micronucleus (MN) assay, while apoptosis was evaluated in nucleated blood cells. The results showed that Cr(III) (CrK(SO4 )2 and CrCl3 ) did not induce any marked genotoxic damage. However, Cr(VI) (CrO3 , K2 Cr2 O7 , Na2 Cr2 O7 , and K2 CrO4 ) produced varying degrees of genotoxicity, with CrO3 being the most potent. MN frequencies increased following 24-h exposure, with a greater effect in male mice. Administering 20 mg/kg of CrO3 via gavage did not lead to significant effects compared to intraperitoneal administration. Short-term oral treatment with a daily dose of 8.5 mg/kg for 49 days elevated MN levels only on day 14 after treatment. Pregnant female mice exposed to CrO3 on day 15 of pregnancy exhibited reduced genotoxic effects compared to nonpregnant animals. However, significant increases in MN levels were found in their fetuses starting 48 h after exposure. In summary, data indicate the potential genotoxic effects of Cr, with Cr(VI) forms inducing higher genotoxicity than Cr(III). These findings indicate that gender, exposure route, and pregnancy status might influence genotoxic responses to Cr.

Effects of green tea polyphenols against metal-induced genotoxic damage: underlying mechanistic pathways.

This review is based upon evidence from the published effects of green tea polyphenols (GTP) on genotoxic damage induced by metals with carcinogenic potential. First, the relationship between GTP and antioxidant defense system is provided. Subsequently, the processes involved in the oxidative stress generated by metals and their relationship to oxidative DNA damage is examined. The review demonstrated that GTP generally decrease oxidative DNA damage induced by exposure to metals such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), chromium (Cr), iron (Fe), and lead (Pb). The pathways involved in these effects are related to: (1) direct scavenging of free radicals (FR); (2) activation of mechanisms to repair oxidative DNA damage; (3) regulation of the endogenous antioxidant system; and (4) elimination of cells with genetic damage via apoptosis. The results obtained in the studies reviewed demonstrate potential for possible use of GTP to prevent and treat oxidative damage in populations exposed to metals. Further, GTP may be considered as adjuvants to treatments for metal-associated diseases related to oxidative stress and DNA damage.

[Antigenotoxicity of the soy isoflavone genistein in mice exposed to carcinogenic hexavalent chromium compounds]. / Antigenotoxicidad de la isoflavona de soya genisteína en ratones expuestos a compuestos cancerígenos del cromo hexavalente.

Introduction: Introduction: the consumption of antioxidant-rich foods such as soy isoflavones may be an alternative in the protection and modulation against metal-induced genotoxicity with carcinogenic potential associated with oxidative stress. Objective: to evaluate the antigenotoxic effects of soy isoflavone genistein in mice exposed to carcinogenic compounds of hexavalent chromium (Cr[VI]). Material and method: twenty-five male Hsd:ICR mice were divided into five groups treated as follows: a) vehicle 1 (sterile distilled water, intraperitoneally); b) vehicle 2 (corn oil for fat-soluble compounds, orally); c) 15 mg/kg of genistein, orally; d) 20 mg/kg of CrO3, intraperitoneally; and e) 15 mg/kg of genistein four hours before the application of 20 mg/kg of CrO3. Evaluations of micronuclei (MN), apoptosis, ratio of polychromatic/normochromatic erythrocytes (EPC/ENC) and cell viability in peripheral blood obtained at 0, 24, 48 and 72 hours were performed. Results: the treatment with genistein reduced MN when administered prior to treatment with CrO3, the effect being greater at 48 hours (reduction of 84 %). Cell viability was reduced with genistein and CrO3 treatments alone, the effect being greater in the latter. Conclusions: genistein effectively blocked the genotoxic action of CrO3. The fact that MN and apoptosis were reduced in the group treated with genistein and CrO3 suggests that genistein could have inhibited the oxidative damage of Cr(VI) since, as there were no cells with damage, the apoptotic pathways were not activated.

Introducción: Introducción: el consumo de alimentos ricos en antioxidantes como las isoflavonas de la soya puede ser una alternativa en la protección y modulación de la genotoxicidad de metales con potencial cancerígeno asociado al estrés oxidativo. Objetivo: evaluar el efecto antigenotóxico de la isoflavona de soya genisteína en ratones expuestos a compuestos cancerígenos de cromo hexavalente (Cr[VI]). Material y método: veinticinco ratones Hsd:ICR macho fueron divididos en cinco grupos tratados de la siguiente forma: a) vehículo 1 (agua destilada estéril, vía-oral); b) vehículo 2 (aceite de maíz para compuestos liposolubles, vía-intraperitoneal); c) 15 mg/kg de genisteína, vía-oral; d) 20 mg/kg de CrO3 vía-intraperitoneal; y e) 15 mg/kg de genisteína cuatro horas antes de la aplicación de 20 mg/kg de CrO3. Se realizaron evaluaciones de micronúcleos (MN), apoptosis, relación de eritrocitos policromáticos/normocromáticos (EPC/ENC) y viabilidad celular en sangre periférica obtenida a las 0, 24, 48 y 72 horas. Resultados: el tratamiento con genisteína redujo los MN cuando fue administrada previamente al tratamiento con CrO3, siendo mayor el efecto a las 48 horas (reducción del 84 %). La viabilidad celular se redujo con los tratamientos de genisteína y CrO3 solos, siendo mayor el efecto en este último. Conclusiones: la genisteína bloqueó eficazmente la acción genotóxica del CrO3. El hecho de que se redujeran los MN y la apoptosis en el grupo tratado con la genisteína y el CrO3 sugiere que la genisteína pudo haber inhibido el daño oxidativo del Cr(VI) ya que, al no haber células con daño, las vías apoptóticas no se activaron.

Catequinas del té verde: efectos antigenotóxicos y genotóxicos. Revisión sistemática / Green tea catechins: antigenotoxic and genotoxic effects. Systematic review

Las catequinas del té verde (Camellia sinensis) (CTV) presentan efectos benéficos para la salud asociados a su potencial antioxidante. Por otra parte, el estrés oxidante es una de las vías de inducción de daño genotóxico. De ahí que, en la presente revisión se realizó un análisis de los efectos antigenotóxicos y genotóxicos de las CTV, haciendo énfasis en las vías implicadas en estos procesos y sus efectos en la salud. Se realizó una revisión de artículos indexados en las bases de datos de PubMed® y Science Direct® (2021) con las palabras clave "green tea" y "green tea catechins". Se delimitaron los estudios utilizando los operadores booleanos "AND", "OR" y "NOT" ("antigenotoxic", "genotoxic", "antioxidant" y "prooxidant"). En su mayoría se consideraron las publicaciones del 2016 al 2021. Se observó que los efectos benéficos en la salud de las CTV están relacionados con: a) su actividad antioxidante mediante la captura, inhibición y prevención de la formación de las especies reactivas de oxígeno; b) la regulación del sistema antioxidante endógeno; c) la activación de los mecanismos de reparación al contribuir en la eliminación del aducto 8-hidroxi-2'-desoxiguanosina; d) la inducción de apoptosis en células con daño al ADN; y e) la inhibición de la inflamación relacionada con su actividad antiapoptótica. Si bien, en algunos de los estudios se reportaron efectos genotóxicos, estos a su vez contribuyeron en la eliminación de células con daño genético, por lo que, no se puede considerar del todo a la actividad genotóxica de las CTV como perjudiciales para la salud(AU)

The green tea catechins (Camellia sinensis) (CTV) have beneficial effects for health associated with their antioxidant potential. Moreover, oxidative stress is one of the pathways for inducing genotoxic damage. Hence, in this review, an analysis of the antigenotoxic and genotoxic effects of CTV was carried out, emphasizing the pathways involved in these processes and their effects on health. A review of articles indexed in the PubMed® and ScienceDirect® (2021) databases with the keywords "green tea" and "green tea catechins" was carried out. Studies were delimited using the Boolean operators "AND", "OR" and "NOT" ("antigenotoxic", "genotoxic", "antioxidant" and "prooxidant"). For the most part, publications from 2016 to 2021 were considered. It was observed that the beneficial health effects of CTVs are related to: a) their antioxidant activity through the capture, inhibition and prevention of the formation of reactive oxygen species; b) the regulation of the endogenous antioxidant system; c) the activation of the repair mechanisms by contributing to the elimination of the 8-hydroxy-2'-deoxyguanosine adduct; d) the induction of apoptosis in cells with DNA damage; and e) the inhibition of inflammation related to its antiapoptotic activity. Although some of the studies reported genotoxic effects, these in turn contributed to the elimination of cells with genetic damage. Therefore, the genotoxic activity of CTV cannot be considered as harmful to health

Protective Effect of Resveratrol against Hexavalent Chromium-Induced Genotoxic Damage in Hsd:ICR Male Mice.

The aim of this study is to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as the possible pathways associated with this protection. Hsd:ICR male mice are divided into groups of the following five individuals each: (a) control 1, distilled water; (b) control 2, ethanol 30%; (c) resveratrol, 50 mg/kg by gavage; (d) CrO3, 20 mg/kg intraperitoneally; (e) resveratrol + CrO3, resveratrol administered 4 h prior to CrO3. The assessment is performed on peripheral blood. Micronuclei (MN) kinetics are measured from 0 to 72 h, while 8-hydroxydeoxyguanosine (8-OHdG) adduct repair levels, endogenous antioxidant system biomarkers, and apoptosis frequency were quantified after 48 h. Resveratrol reduces the frequency of Cr(VI)-induced MN and shows significant effects on the 8-OHdG adduct levels, suggesting that cell repair could be enhanced by this polyphenol. Concomitant administration of resveratrol and Cr(VI) results in a return of the activities of glutathione peroxidase and catalase to control levels, accompanied by modifications of superoxide dismutase activity and glutathione levels. Thus, antioxidant properties might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant genotoxicity. The increase in apoptotic cells and the decrease in necrosis further confirmed that resveratrol effectively blocks the actions of Cr(VI).

Vanadium oxides modify the expression levels of the p21, p53, and Cdc25C proteins in human lymphocytes treated in vitro.

In vitro assays have demonstrated that vanadium compounds interact with biological molecules similar to protein kinases and phosphatases and have also shown that vanadium oxides decrease the proliferation of cells, including human lymphocytes; however, the mechanism, the phase in which the cell cycle is delayed and the proteins involved in this process are unknown. Therefore, we evaluated the effects of vanadium oxides (V2 O3 , V2 O4 and V2 O5 ) in human lymphocyte cultures (concentrations of 2, 4, 8, or 16 µg/ml) on cellular proliferation and the levels of the p53, p21 and Cdc25C proteins. After 24 h of treatment with the different concentrations of vanadium oxides, the cell cycle phases were determined by evaluating the DNA content using flow cytometry, and the levels of the p21, p53 and Cdc25C proteins were assessed by Western blot analysis. The results revealed that the DNA content remained unchanged in every phase of the cell cycle; however, only at high concentrations did protein levels increase. Although, according to previous reports, vanadium oxides induce a delay in proliferation, DNA analysis did not show this occurring in a specific cell cycle phase. Nevertheless, the increases in p53 protein levels may cause this delay.

Antigenotoxic effects of (-)-epigallocatechin-3-gallate (EGCG) and its relationship with the endogenous antioxidant system, 8-hydroxydeoxyguanosine adduct repair (8-OHdG), and apoptosis in mice exposed to chromium(VI).

This study aimed to investigate the relationship between endogenous antioxidant system, 8-hydroxydeoxyguanosine adduct (8-OHdG) repair, and apoptosis in mice treated with chromium(VI) alone and in the presence of the antigenotoxic compound (-)-epigallocatechin-3-gallate (EGCG). Groups of 5 Hsd:ICR male mice were divided and treated as follows: (1) control, vehicle only; (2) EGCG, 8.5 mg/kg by gavage alone; (3) CrO3, 20 mg/kg intraperitoneally alone; and (4) EGCG combined with CrO3, EGCG was administered 4 hr prior to CrO3. Peripheral blood parameters were analyzed before treatment administration (time 0), and 48 hr after exposure. The administration of EGCG increased 8-OHdG levels and superoxide dismutase (SOD) activity. Treatment with CrO3 increased number of micronucleus (MN) presence, elevated apoptotic/necrotic cells frequencies, decreased 8-OHdG levels, diminished total antioxidant capacity (TAC), increased glutathione (GSH) total levels, and lowered SOD activity. Administration of EGCG prior to treatment with CrO3 resulted in lower concentrations of MN, reduced apoptotic and necrotic cell number, and restored TAC and SOD activity to control levels. It is conceivable that the dose of EGCG plays an important role in the genotoxic damage protection pathways. Thus, this study confirms the action of EGCG as an antigenotoxic agent against chromium(VI)-induced oxidative insults and demonstrates potential protective pathways for EGCG actions to counteract genotoxic damage induced by this metal.

[The role of resveratrol on heavy metal-induced oxidative stress]. / El papel del resveratrol sobre el estrés oxidante inducido por metales pesados.

INTRODUCTION: Introduction and objetives: oxidative stress is considered one of the main mechanisms of genotoxicity and carcinogenicity of heavy metals. In contrast, resveratrol has antioxidant properties and is one of the most studied polyphenols due to its wide variety of beneficial health effects. However, there are no systematic reviews of the scientific literature in which the effects of resveratrol on oxidative stress induced by heavy metals are analyzed. Methods: in this review, articles were searched using the PubMed and ScienceDirect databases (1996-2018). After applying various filters, eleven in vivo and in vitro researches were considered, in which the effects of resveratrol on oxidative stress induced by arsenic (As), cadmium (Cd), copper (Cu), chromium (Cr) and iron (Fe) were studied. Results: this review presents an analysis of the chemical effects of resveratrol on oxidative stress associated with the exposure of metal compounds. The interaction of resveratrol with the production of reactive oxygen species (ERO's), the endogenous antioxidant system and its effects on DNA damage is discussed. From these studies, a diagram that shows the proposed interactions for resveratrol; heavy metals As, Cd, Cu, Cr and Fe; and oxidative stress is generated. Conclusions: the studies analyzed show that resveratrol is able to modulate the oxidative stress generated by different heavy metal compounds such as As, Cd, Cu, Cr and Fe.

INTRODUCCIÓN: Introducción y objetivos: el estrés oxidante es considerado uno de los principales mecanismos de genotoxicidad y carcinogenicidad de los metales pesados. Por otra parte, el resveratrol posee propiedades antioxidantes y es uno de los polifenoles más estudiados debido a su gran variedad de efectos benéficos para la salud. Sin embargo, no hay revisiones sistemáticas de la literatura científica en las que se analicen los efectos del resveratrol sobre el estrés oxidante inducido por metales pesados. Métodos: en esta revisión, se realizó una búsqueda de artículos mediante las bases de datos PubMed y ScienceDirect (1996-2018). Después de aplicar diversos filtros, se consideraron once investigaciones in vivo e in vitro, en las que se estudiaron los efectos del resveratrol sobre el estrés oxidante inducido por el arsénico (As), cadmio (Cd), cobre (Cu), cromo (Cr) y hierro (Fe). Resultados: en la revisión se presenta un análisis de los efectos químicos del resveratrol sobre el estrés oxidante asociado a la exposición de compuestos metálicos. Se discute la interacción del resveratrol con la producción de especies reactivas de oxígeno (ERO's), el sistema antioxidante endógeno y sus efectos sobre el daño al ADN. A partir de estos estudios se genera un diagrama que muestra las interacciones propuestas para el resveratrol; los metales pesados As, Cd, Cu, Cr y Fe; y el estrés oxidante. Conclusiones: los estudios analizados muestran que el resveratrol es capaz de modular el estrés oxidante generado por diferentes compuestos de metales pesados como los As, Cd, Cu, Cr y Fe.

Phosphorylated ATM and H2AX in T and B lymphocytes from rats with moderate and severe malnutrition.

Protein calorie malnutrition (PCM) occurs when insufficient nutrients are consumed to satisfy the biological needs of an organism. The literature supports the relationship between malnutrition and DNA damage, and among the injuries to genetic material, DNA double-strand breaks (DSBs) are the most dangerous. This study aimed to determine whether the ability of splenic and peripheral blood T and B lymphocytes from nursing rats to recognize DSB-induced DNA damage is affected by PCM. Wistar strain rats were used, and experimental malnutrition was induced by creating food competition during lactation by increasing the number of offspring per wet nurse. Due to its high specificity, the phosphorylated H2AX variant histone assay associated with pATM (Ser1981) combined with flow cytometry was herein used to demonstrate the impact of malnutrition on the DNA damage response. Flow cytometry data indicated that splenic T and B lymphocytes from rats with severe PCM have the capacity to detect genetic material damage, as shown by an increased number of pATM + cells and altered signaling pathway continuity. Collectively, these data suggest that severe malnutrition compromises the continuity of the DNA damage response.

Trimethoprim-sulfamethoxazole treatment increases the Pig-a mutant frequency in peripheral blood from severely malnourished rats.

Severe malnutrition is a complex condition that increases susceptibility to infections. Thus, drugs are extensively used in malnutrition cases. In the present study, we assessed the mutagenic effects of combined trimethoprim and sulfamethoxazole (TMP-SMX) treatment in undernourished (UN) and well-nourished (WN) rats. Six-week-old UN and WN Han-Wistar rats were treated with TMP-SMX at a daily dose of 10 mg/kg/d TMP and 50 mg/kg/d SMX for 5 or 10 days. Blood was collected from the tail vein one day before (day -1) and 15, 30, and 45 days after TMP-SMX administration. The Pig-a mutant frequencies (MFs) in peripheral blood reticulocytes (RETs) and erythrocytes (RBCs) were measured through flow cytometry. Severe malnutrition increased the basal MFs in RETs (RET CD59-) and RBC (RBCs CD59-). These findings support the hypothesis that severe malnutrition is mutagenic even in the absence of exposure to an exogenous mutagen. UN and WN rats treated for 5 or 10 consecutive days with TMP-SMX had significantly increased and sustained Pig-a mutant frequencies, demonstrating the mutagenic effects of this drug.

In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice.

This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5.

Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity.

This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage.

[IN VIVO EFFECT OF RED WINE UNDILUTED, DILUTED (75%) AND ALCOHOL-FREE ON THE GENOTOXIC DAMAGE INDUCED BY POTENTIAL CARCINOGENIC METALS: CHROMIUM [VI]]. / EFECTO IN VIVO DEL VINO TINTO SIN DILUIR, DILUIDO (75%) Y SIN ALCOHOL SOBRE EL DAÑO GENOTÓXICO INDUCIDO POR METALES PESADOS CON POTENCIAL CANCERÍGENO: CROMO [VI].

INTRODUCTION: the carcinogenesis may be initiated and promoted by the oxidative DNA damage. The compounds of chrome (Cr [VI]) cause oxidative stress (EOx) and are recognized as carcinogens in humans. In this sense, it is proposed that drinks with a high antioxidative potential, such as red wine, may have protective or modulatory effects on the oxidative DNA damage. OBJECTIVE: to study the effects of the administration in vivo of undiluted, diluted (75%) and alcohol-free red wine on the genotoxic damage induced by carcinogenic metals (Cr [VI]), by evaluating the micronucleus (MN) in polychromatic erythrocytes (EPC) in mice (CD-1). MATERIAL AND METHOD: it was randomly organized the follow groups: (i) control, (ii) undiluted, diluted and alcohol-free red wine (free access), (iii) CrO3 (20 mg/kg by intraperitoneal route) and (iv) CrO3-red wine. The evaluations were made in blood samples obtained from the caudal vein, in which it was identified the MN and EPC before, during and after treatments. RESULTS AND DISCUSSION: the red wine (diluted and alcohol-free) was capable of decreasing the averages of MN induced by CrO3, demonstrating its modular capacity in vivo in the oxidative DNA damage caused by EOx-induced carcinogens. The administration of only undiluted red wine presented toxic effects. CONCLUSIONS: our results raises expectations on the use of substances like the red wine for the protection or modulation of genotoxic damage, encouraging its application in the carcinogenic and mutagenic processes.

Introducción: la carcinogénesis puede ser iniciada y promovida por el daño oxidativo al ADN. Los compuestos de cromo (Cr) [VI] generan estrés oxidativo (EOx) y son reconocidos como cancerígenos en humanos. En este sentido, se plantea que bebidas que presentan un alto potencial antioxidante, como el vino tinto, pudieran tener efectos protectores o moduladores del daño oxidativo al ADN. Objetivo: estudiar los efectos de la administración in vivo de vino tinto sin diluir, diluido (75%) y sin alcohol, sobre el daño genotóxico inducido por metales cancerígenos (Cr [VI]), mediante la evaluación de micronúcleos (MN) en eritrocitos policromáticos (EPC) de ratones (CD-1). Material y método: se conformaron aleatoriamente los siguientes grupos: (i) testigo, (ii) vino tinto sin diluir, diluido o sin alcohol (libre acceso), (iii) CrO3 (20 mg/kg por vía intraperitoneal) y (iv) vino tinto-CrO3. Las evaluaciones se realizaron en muestras de sangre obtenidas de la vena caudal, en las que se identificaron los MN en EPC antes, durante y después de los tratamientos. Resultados y discusión: el vino tinto (diluido y sin alcohol) fue capaz de disminuir los promedios de MN inducidos por el CrO3, lo que muestra su capacidad para modular in vivo el daño oxidativo al ADN causado por cancerígenos inductores de EOx. La administración únicamente de vino tinto sin diluir presentó efectos tóxicos. Conclusiones: nuestros resultados generan expectativas sobre el empleo de sustancias como el vino tinto en la protección o modulación del daño genotóxico, lo que podría conducir a su aplicación en los procesos de carcinogénesis y mutagénesis.

Antigenotoxic effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on chromium trioxide-induced micronuclei in the polychromatic erythrocytes of mouse peripheral blood.

This study was conducted to investigate the modulating effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on the genotoxic damage induced by Cr(VI) in polychromatic erythrocytes of CD-1 mice. The animals were divided into the following groups: (i) vehicle only; (ii) flavonoids (10 mg/kg EGCG, 100 mg/kg quercetin, 625 mg/kg rutin, or 100-625 mg/kg quercetin-rutin); (iii) Cr(VI) (20 mg/kg of CrO3); and (iv) flavonoids concomitantly with Cr(VI). All of the treatments were administered intraperitoneally (i.p.). The genotoxic damage was evaluated based on the number of micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein 0, 24, 48, and 72 h after treatment. Groups treated with EGCG and quercetin exhibited no significant statistical changes in induction of MN-PCE. However, CrO3 treatment significantly increased MN-PCE induction 24 and 48 h after injection. Treatment with flavonoids prior to CrO3 exposure decreased MN-PCE induction compared with CrO3 only. The magnitudes of the potency of flavonoids were in the following order: rutin (82%) > quercetin (64%) > quercetin-rutin (59%) and EGCG (44%). The group treated with rutin significantly reduced genotoxic damage in mice treated with Cr(VI) (antioxidant effect). However rutin exerted a marginal genotoxic effect when administered alone (pro-oxidant effect). Our findings suggest protective effects of EGCG, quercetin, and rutin against genotoxic damage induced by Cr(VI).

Antigenotoxic and apoptotic activity of green tea polyphenol extracts on hexavalent chromium-induced DNA damage in peripheral blood of CD-1 mice: analysis with differential acridine orange/ethidium bromide staining.

This study was conducted to investigate the modulating effects of green tea polyphenols on genotoxic damage and apoptotic activity induced by hexavalent chromium [Cr (VI)] in CD-1 mice. Animals were divided into the following groups: (i) injected with vehicle; (ii) treated with green tea polyphenols (30 mg/kg) via gavage; (iii) injected with CrO3 (20 mg/kg) intraperitoneally; (iv) treated with green tea polyphenols in addition to CrO3. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCEs) obtained from peripheral blood at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. Treatment of green tea polyphenols led to no significant changes in the MN-PCEs. However, CrO3 treatment significantly increased MN-PCEs at 24 and 48 h after injection. Green tea polyphenols treatment prior to CrO3 injection led to a decrease in MN-PCEs compared to the group treated with CrO3 only. The average of apoptotic cells was increased at 48 h after treatment compared to control mice, suggesting that apoptosis could contribute to eliminate the DNA damaged cells induced by Cr (VI). Our findings support the proposed protective effects of green tea polyphenols against the genotoxic damage induced by Cr (VI).